Humans and other mammals, including many types of domesticated animals from dairy cattle to the family cat, are plagued by ringworm (dermatomycosis) which is caused by infection by one or more of a number of parasitic fungi generically called "dermatophytes" (i.e., organisms which upon infection cause ringworm). Dermatophytes include without limitation the species listed in Table I.
TABLE I ______________________________________ Dermatophytes and Hosts Dermatophyte Host(s) ______________________________________ Epidermophyton floccusum man Microsporum audouini man (children), dogs, monkeys Microsporum canis dogs, cats, man, sheep, monkeys, swine Microsporum distortum monkeys, dogs Microsporum equinum horses Microsporum gypseum (gypsum) man, dogs, cats, horses Microsporum nanum swine Trichophyton concentricum man Trichophyton equinum man (children), horses Trichophyton gallinae poultry, man Trichophyton gypsum (gypseum) sheep Trichophyton megnini man, cattle Trichophyton mentagrophytes mice, rats, muskrats, chinchillas, cattle, man, horses, sheep, dogs, cats, swine, goats, rabbits, guinea pigs Trichophyton quinckeanum (quinkeanum) man, horses, sheep Trichophyton rubrum dogs, swine, foxes, primates, mice, squirrels, muskrats, Trichophyton schoenleini man, cats, mice, rats, rabbits Trichophyton tonsurans man Trichophyton verrucosum cattle, man, horses, dogs, sheep Trichophyton verrucosum var. album cattle Trichophyton verrucosum var. discoides cattle, swine Trichophyton verrucosum var. ochraceum sheep Trichophyton violaceum man ______________________________________
Extensive additional information relating to dermatophytes and dermatophyte mycology can be found in "The Medical Mycology Handbook" by Campbell and Stewart (John Wiley & Sons, 1980) (hereinafter the "Campbell/Stewart Handbook"), which is incorporated herein by reference as if fully set forth.
Ringworm usually manifests itself as a series of rapidly expanding, irritating lesions which can occur in any area of the skin. Dermatophytes attack chiefly keratinized tissues, particularly the stratum corneum and hair fibers resulting in autolysis of the fiber structure, breaking off of the hair and alopecia. Exudation from invaded epithelial layers, epithelial debris and fungal hyphae produce the dry crusts characteristic of the disease. The lesions progress if suitable environmental conditions for mycelial growth exist, including a warm humid atmosphere, and a slightly alkaline pH of the skin. Dermatophytes are all strict aerobes and the fungi die out under the crust in the center of most lesions leaving only the periphery active. It is this mode of growth which produces the centrifugal progression and the characteristic ring form of the lesions (hence "ring-worm"). Secondary bacterial invasion of hair follicles and other tissues is also commonly associated with ringworm infection.
Many common ailments are actually dermatophyte infections. Tinea pedis (athlete's foot or ringworm of the feet) is associated with Epidermophyton floccusum, various species of Trichophyton and, rarely, species of Microsporum and other fungi. Tinea unguium (ringworm of the nails) is caused by Trichophyton rubrum. Tinea cruris ("Jock itch" of ringworm of the groin) results from infection with Epidermophyton floccusum and species of Trichophyton. Tinea corporis (ringworm of the body) is caused by various species of Trichophyton and Microsporum, involves the smooth and hairless skin and results in either simple scaling or deep granulomas. Tinea imbricata (scaly ringworm) is a disease of the tropics and is apparently caused by a single fungus, Trichophyton concentricum. Tinea barbae (barber's itch or ringworm of the beard) is caused by various species of Trichophyton and Microsporum. Tinea capitis (ringworm of the scalp and hair) is most common in children but may affect adults. The causative organisms, various species of Trichophyton and Microsporum, may be acquired by contact with infected animals or children. Microsporum audouini is most commonly involved but Microsporum canis and Microsporum gypsum (gypseum) produce deeper, more severe lesions. Trichophyton tonsurans is also known to produce widespread infections in the scalp.
To date, the ringworm problem has, for the most part, been handled by post-infection treatment because an effective vaccine has not been available. The significance of skin pH in the development of ringworm is widely known. The susceptibility of humans to ringworm is much greater before puberty than afterwards when the skin pH falls from about 6.5 to about 4.0. This change is largely due to excretion of fatty acids in the sebum and these fatty acids are often highly fungistatic. For this reason, various kinds of topically-applied agents have been used to kill the infecting fungus and relieve the condition. Many treatments for ringworm are based upon alteration of skin pH by topically applying various agents (e.g., propionic acid, undecylenic acid). Other ringworm therapies have relied upon other topically applied commercially available products such as Conofite and Captan. Orally-administered agents (e.g., Griseofulvin and Ketoconazole) are also available.
Unfortunately, however, post-infection treatment cannot completely prevent in many instances. Once therapy is discontinued, reinfection usually occurs. It would therefore be desirable to provide a vaccine for ringworm to prevent infection before these adverse effects are suffered. One of the objects of the present invention is to provide such a vaccine.